Department of Pharmacology, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.
Neurosci Lett. 2012 Jul 11;521(1):62-6. doi: 10.1016/j.neulet.2012.05.060. Epub 2012 May 30.
Lithium is licensed for the treatment of bipolar disorders and also discussed in relation to neuroprotective properties. Although the drug has a small therapeutic window, its uptake and passage into the brain are poorly understood. We administered lithium to rats, following an acute (3 mmol/kg, i.p.) or chronic (3 mmol/kg/day, p.o.) regime. Lithium levels were assessed in serum, brain homogenate, cerebrospinal fluid (CSF) and, by means of microdialysis, in the extracellular space (ECS) of the brain 2, 6 and 24h post injection or after 3 weeks of chronic administration. Lithium is detected in brain ECS within minutes of administration and reaches maximum levels in brain extracellular fluid after 30 min. In the early phase after lithium administration (2 and 6h), serum levels of lithium do not differ significantly from those assessed in CSF and brain homogenate. Afterwards, however, accumulation in brain tissue occurs. As a consequence, after 24h and 3 weeks, lithium levels in brain homogenate (i.e., intracellular levels) are significantly higher than in CSF or dialysates (i.e., extracellular levels). In conclusion, lithium rapidly reaches the brain, but after prolonged treatment, brain intracellular levels are high and poorly represented by plasma or CSF measurements.
锂被批准用于治疗双相情感障碍，并在神经保护特性方面进行了讨论。尽管该药物的治疗窗较窄，但人们对其摄取和进入大脑的过程仍了解甚少。我们给大鼠施用锂，采用急性（3mmol/kg，腹腔内注射）或慢性（3mmol/kg/天，口服）方案。在注射后 2、6 和 24 小时或慢性给药 3 周后，评估血清、脑匀浆、脑脊液（CSF）以及通过微透析在大脑细胞外空间（ECS）中的锂水平。给药后几分钟内即可在脑 ECS 中检测到锂，并在 30 分钟后在脑细胞外液中达到最高水平。在锂给药后的早期阶段（2 和 6 小时），血清中的锂水平与 CSF 和脑匀浆中的锂水平无显著差异。然而，随后会在脑组织中积累。因此，在 24 小时和 3 周后，脑匀浆中的锂水平（即细胞内水平）明显高于 CSF 或透析液中的水平（即细胞外水平）。总之，锂迅速到达大脑，但在长期治疗后，大脑细胞内水平较高，而血浆或 CSF 测量值则不能很好地反映。
